Applying Quality Improvement Methodology to Standardize Pediatric Urinary Tract Infection Diagnosis and Management throughout a Healthcare System

Background: Pediatric urinary tract infections (UTIs) require early diagnosis and appropriate treatment to avoid short- and long-term morbidity. Baseline data from 13,000 children across a regional health system demonstrated wide variation in UTI management, including antibiotic choice, duration, and dosing. In 2019, the local antibiotic stewardship team recommended cephalexin as the ideal first-line UTI treatment due to its effectiveness, narrow spectrum, low cost, and palatability. This project aimed to improve first-line prescription of cephalexin as an empiric antibiotic treatment for uncomplicated UTIs from 34% to 75% in children 60 days to 18 years of age presenting to any site within the healthcare system within 6 months. Methods: A multidisciplinary team of key stakeholders reviewed baseline data and developed three key drivers. These included a standardized UTI pathway, electronic health record enhancements, and provider education. Interventions were supported by a literature review and implemented via Plan-Do-Study-Act cycles with data monitored bimonthly. The primary outcome was the percentage of patients prescribed cephalexin for presumed UTI over the total number of presumed UTI diagnoses treated with empiric antibiotics throughout the healthcare system. The balancing measure included 14-day return visits for a UTI-related diagnosis across the system. Results: After the release of the updated UTI pathway, first-line cephalexin prescribing for UTI improved from 34% to 66%. There was no change in 14-day revisits for UTI. Conclusions: Standardizing the diagnosis and management of UTIs across the spectrum of coordinated care led to improved system-wide adherence to local antibiotic stewardship guidelines for empiric UTI treatment.

The UTI Pathway team made the decision to remove race as a risk factor, due to the evolving understanding of the role of racial inequality in healthcare and lack of a clear biological basis for race as a risk factor for UTI (Kowalsky et al, 2020;Vyas et al, 2020).In this context, utilizing race as a factor in the clinical decision-tools risks perpetuating the same inequalities that generated these data in the first place.The team acknowledges the utility of UTICalc as a tool to aid provider decision-making but recommends that non-black be selected for all patients, in order to reduce the potential risk for racial bias.
Return to: Outpatient Testing and Empiric Treatment

Appendix: Cephalexin for UTI Rationale
In assessing our local antibiogram using CLSI urine specific breakpoints, the chosen concentrations at which bacteria are considered susceptible or resistant to a specific antibiotic, the antimicrobial stewardship program determined cephalexin is the narrowest spectrum antibiotic that could empirically cover the majority of likely pathogens.Although cefdinir has frequently been prescribed to treat outpatient UTIs in our system, it is unnecessarily broad for the treatment of common urinary pathogens (Table 1).Additionally, the pharmacokinetic profile of cefdinir is inferior to cephalexin.
Cephalexin has significantly higher bioavailability and less protein binding than cefdinir, though does require a more frequent dosing schedule due to its short half-life (Table 2).Although trimethoprim-sulfamethoxazole is another commonly used agent for outpatient UTI treatment, our antibiogram reveals lower coverage for Escherichia coli compared to cephalosporins when accounting for urine specific breakpoints.
The Clinical and Laboratory Standards Institute (CLSI) created urine specific breakpoints for enterobacteriaceae in 2014. 1 These breakpoints predict susceptibility for cefazolin for the most common urine pathogens (Escherichia coli, Klebsiella Pneumoniae, and Proteus mirabilis) at a higher minimum inhibitory concentration (MIC) than non-urine specimens.Furthermore, cefazolin may be used as a surrogate to predict susceptibility to other cephalosporin antibiotics (i.e., cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime, cephalexin, and loracarbef) (Table 1).* Using the CLSI urine-specific breakpoints which can be used as a surrogate to predict susceptibility to other cephalosporin antibiotics (i.e., cefaclor, cefdinir, cefpodoxime, cefprozil, cefuroxime, cephalexin, and loracarbef) ** Ceftriaxone breakpoints cannot be directly used to predict susceptibility to cefdinir.There are cefdinir specific breakpoints for Enterobacteriaceae, but it is not on the CHW susceptibility panel.When cefazolin is used as a surrogate for oral cephalosporins and interpreted using the uncomplicated UTI breakpoints for E. coli, Kleb pneumo and P. mirabilis, cefdinir resistance may be overcalled.Cefdinir may also be susceptible when cefazolin is reported as resistant.

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Medicine is a dynamic science; as research and clinical experience enhance and inform the practice of medicine, changes in treatment protocols and drug therapies are required.The authors have checked with sources believed to be reliable in their effort to provide information that is complete and generally in accord with standards accepted at the time of publication.However, because of the possibility of human error and changes in medical science, neither the authors nor Children's Hospital and Health System, Inc. nor any other party involved in the preparation of this work warrant that the information contained in this work is in every respect accurate or complete, and they are not responsible for any errors in, omissions from, or results obtained from the use of this information.Readers are encouraged to confirm the information contained in this work with other sources.

UTI Risk Stratification: Age >60 days to <2 years Female Risk Factors:
After diagnosis with febrile UTI/pyelonephritis, patients and families should receive education about the importance of seeking prompt medical evaluation (within 48 hours) for future febrile illnesses Outpatient Testing and Empiric Treatment Clinical Follow-Up and Imaging Recommendations  Check sensitivities, change antibiotic if necessary*  See imaging and follow-up recommendations Contaminant or negative  Stop treatment  Inform family that child did not have  No treatment  Inform family that child did not have UTI *If clinical symptoms are improving, it is not necessary to change antibiotics, even if culture sensitivities show resistance For questions concerning this work, contact UTIPathway@chw.org©2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026 Clinical Follow-Up and Imaging Recommendations   Goal of imaging in febrile UTI/pyelonephritis: to identify patients with vesicoureteral reflux (VUR) and to rule out the small percentage (~1%) of patients with structural anomalies of the urinary tract  Imaging is not typically indicated for recurrent, non-febrile UTIs, unless there are other symptoms (i.e.gross hematuria or recurrent flank pain) or the patient has recurrent (≥3/year) UTIs with the same organism(s) concerning for nidus, such as stone When to Obtain a Renal and Bladder Ultrasound (RBUS) When to Obtain a Voiding Cystourethrogram (VCUG) Urology Referral Recommendations (all ages)  A Referral to Urology should be placed for: o Boys after the 1 st febrile UTI/pyelonephritis, irrespective of imaging results o Girls after the 1 st febrile UTI/pyelonephritis, with abnormal imaging* o Boys and Girls after the 2 nd febrile UTI/pyelonephritis, irrespective of imaging results o Consider an outpatient referral for boys or girls after the 1 st febrile UTI/pyelonephritis, if UTI required inpatient evaluation o Desire by the family or the primary provider to seek specialist evaluation following the 1 st febrile UTI/pyelonephritis  The Urology Consult can be performed as an e-consult or in-person consult, based on family and provider preferences Outpatient Testing and Empiric Treatment Interpreting Urine Culture Results st febrile UTI/pyelonephritis plus any of the following:  Non-E.Coli UTI  Parent or sibling with VUR  High provider index of suspicion for clinically significant VUR, including severe presentation of febrile UTI (i.e.prolonged or complicated admission) or multi-drug resistant organism  Parental concern and desire to evaluate for VUR For questions concerning this work, contact UTIPathway@chw.org©2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026Appendix:

CW Clean Void Urine Specimen teaching sheets
For questions concerning this work, contact UTIPathway@chw.org©2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026 Appendix: Appendix: Additional Testing Considerations for Sexually Active Adolescents  For males: obtain first void ('dirty') urine specimen for Gonococcus (GC)/Chlamydia (Chl) testing  For females: obtain vaginal self-swab or first void urine specimen for Gonococcus (GC)/Chlamydia (Chl) testing; consider pregnancy testing  Obtain clean void specimen for UA +/-Urine Culture  For males and females: Consider HSV testing if visible lesions; consider Syphilis Screen if GC/Chl positive Return to: Outpatient Testing and Empiric Treatment Appendix: Leukocyte Esterase vs Leukocytes  The value that CW lab reports as 'Leukocytes' is a direct reference to 'Leukocyte esterase' Return to: Outpatient Testing and Empiric Treatment For questions concerning this work, contact UTIPathway@chw.org©2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026Appendix:

Clinical Differentiation between Cystitis and Pyelonephritis
For questions concerning this work, contact UTIPathway@chw.org© 2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026

Table 2 . Comparison of pharmacokinetic profiles of cefdinir and cephalexin
Failed outpatient therapy as defined by persistent clinical symptoms or lack of meaningful clinical improvement beyond 48 hours on appropriate antimicrobial therapy  In the event of treatment failure, consider: Version History and Summary of Changes  Version 1.0 (4/5/2021): Go-Live For questions concerning this work, contact UTIPathway@chw.org© 2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026 For questions concerning this work, contact UTIPathway@chw.org© 2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026 Appendix: Treatment Failure  For questions concerning this work, contact UTIPathway@chw.org© 2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026 For questions concerning this work, contact UTIPathway@chw.org© 2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026 For questions concerning this work, contact UTIPathway@chw.org© 2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026 For questions concerning this work, contact UTIPathway@chw.org© 2018 Children's Hospital and Health System, Inc. See Medical Disclaimer Updated: March, 2021 Valid until: March, 2026